Airway Surface Liquid pH Regulation in Airway Epithelium Current Understandings and Gaps in Knowledge

Abstract

Knowledge on the mechanisms of acid and base secretion in airways has progressed recently. The aim of this review is to summarize the known mechanisms of airway surface liquid (ASL) pH regulation and their implication in lung diseases. Normal ASL is slightly acidic relative to the interstitium, and defects in ASL pH regulation are associated with various respiratory diseases, such as cystic fibrosis. Basolateral bicarbonate (HCO3−) entry occurs via the electrogenic, coupled transport of sodium (Na+) and HCO3−, and, together with carbonic anhydrase enzymatic activity, provides HCO3− for apical secretion. The latter mainly involves CFTR, the apical chloride/bicarbonate exchanger pendrin and paracellular transport. Proton (H+) secretion into ASL is crucial to maintain its relative acidity compared to the blood. This is enabled by H+ apical secretion, mainly involving H+/K+ ATPase and vacuolar H+-ATPase that carry H+ against the electrochemical potential gradient. Paracellular HCO3− transport, the direction of which depends on the ASL pH value, acts as an ASL protective buffering mechanism. How the transepithelial transport of H+ and HCO3− is coordinated to tightly regulate ASL pH remains poorly understood, and should be the focus of new studies.

Respiratory Infections Early-Stage Medication: Inhalation Formulation & Dosage of PVP Iodine

“…Consequently, even a 1/10 dilution with water does not change much the pH level [32]. pH values below 7.0 decrease ciliary beating in vitro (50% at pH = 5.5 and almost 100% at pH = 3.5) [33]. We speculate that when sensitivity of ciliated cells to PVP-I solutions was found in various tests or clinical trials, it was due to the pH of the solution and not the iodine.…”

Inhalation Formulation & Dosage of PVP Iodine for Respiratory Infections Treatment

“…Consequently, even a 1/10 dilution with water does not change much the pH level [32]. pH values below 7.0 decrease ciliary beating in vitro (50% at pH = 5.5 and almost 100% at pH = 3.5) [33]. Hence, we speculate that when sensitivity of ciliated cells to PVP-I solutions was found in various tests or clinical trials, it was due to the pH of the solution and not the iodine (as far as we know, this suggestion is not stated in the literature).…”

A review of cystic fibrosis: Basic and clinical aspects

“…ATP12A mediates the electroneutral exchange of H + for potassium (K + ) but may also function in a Na + /K + exchange mode. 48 In humans lacking CFTR, unchecked H + secretion by the nongastric H + /K + adenosine triphosphatase (ATP12A) acidified airway surface liquid, which impaired airway host defenses. However, the expression of ATP12A is low in murine airways, which may partly explain the very mild pulmonary phenotype in murine models of CF.…”